Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000818214 | SCV000958815 | uncertain significance | Aortic aneurysm, familial thoracic 4 | 2021-05-31 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine with phenylalanine at codon 1692 of the MYH11 protein (p.Leu1692Phe). The leucine residue is highly conserved and there is a small physicochemical difference between leucine and phenylalanine. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with MYH11-related disease. This variant is present in population databases (rs754570649, ExAC 0.001%). |
Color Diagnostics, |
RCV001189309 | SCV001356573 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2023-05-16 | criteria provided, single submitter | clinical testing | This missense variant replaces leucine with phenylalanine at codon 1692 of the MYH11 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with MYH11-related disorders in the literature. This variant has been identified in 3/282896 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |